Pressure reversal of anesthesia indicates an excess volume increase of the total system during anesthesia. This excess volume is unrelated to the expansion of membrane structure postulated by the membrane stabilization concept. We recognize anesthesia as a nonspecific change of physical properties involving the membrane/water interface as well as the membrane structure. The binding of anesthetics to phospholipid membranes may not be simple isotropic solvation of anesthetic molecules into the lipid domain. Presumably dipolar inhalation anesthetics partition into the interfacial region of the cell membrane and decrease the dielectric constant of the interface. This would decrease electrostatic and dipolar forces exerted on the water dipole and release the high-density interfacial water, increasing total volume. It also decreases the hydrophilicity of the interface, and the flux of hydrated ions through the dehydrated membrane may become sluggish. This project is aimed at investigation of the physical properties of lipid membranes and their interfaces together with those of anesthetic molecules. The volume of the system will be measured by solution densimetry of vesicle suspension. Differential scanning calorimetry and optical method are used to study the phase transition of lipid membranes. With monolayers, surface tension is used the phase transition of lipid membranes. With monolayers, surface tension is used to study the energetics of penetration of anesthetics to the membrane. Surface viscosity provides data on the true membrane fluidity, and is used to study the water/membrane interaction. A membrane conductance study, which was proposed as one of the long range objectives in the original proposal, is now included in the present project to relate the observed changes of the physical properties of the model membrane to the electrogenesis of the bilayer membrane. The ultimate objective is to elucidate the molecular mechanism that relates membrane physical properties to excitation.